MR. GREEN GENES
William Haseltine Sees the Future In His Labs
By Linton Weeks
Washington Post Staff Writer
Tuesday, February 17, 1998; Page E01
washingtonpost.com;
In the eerie light that shines through the X-ray, William Haseltine dreams.
He likes what he sees. This is it. Further proof that healthy genes can help the human body repair itself. That such genes can be identified and then reproduced countless times. That the world will someday know he's not a money-mad, social-climbing, beaker-brandishing lunatic in a lab coat. And that his creation, Human Genome Sciences in Rockville, could become a multi-billion-dollar pharmaceutical company in the century soon to come.
The X-ray in question shows the lower leg of a 61-year-old woman. The limb is a mess. The patient is in constant pain. The three main arteries that carry blood into the leg are missing. Vanished. Kaput. Fatty acids choked the blood flow; the arteries withered away. So did the smaller blood vessels that depended on the arteries.
Posted on a light box at St. Elizabeth's Medical Center in Boston, the film portrays a large solid-black mass with no crisscrossing lines. Next to it, on the right, is another X-ray of the same leg after 12 weeks of treatment using healthy genes, the kind Haseltine can concoct in his lab. The leg is alive. Vessels loop, swoop and swirl.
Standing beside Haseltine is Jeffrey Isner, chief of cardiovascular research at St. Elizabeth's. A soft-spoken, tousle-haired doc, Isner has discovered a simple and direct way to inject the healthy gene, called VEGF-1, directly into the muscle. He has signed an agreement with Haseltine. Human Genome Sciences will replicate the genes; Isner will teach people the world over how to use it.
Isner stands to make millions of dollars from this arrangement. Haseltine could make much more. He is cutting deals around the world with folks like Isner, folks who believe that the 21st century will see the dawn of a new age, folks who are betting everything that gene-based drugs will be able to cure diseases, heal wounds, restore lost hair and Lord knows what else, folks who will buy the genes they need from Haseltine's labs.
Patting his slicked-back black hair, Haseltine gazes at the X-rays. To no one and to the world he says, "This is what makes me happy."
Rhymes With 'Dazzle Gene'
One part scientist, one part aesthete, one part socialite and all business, William Haseltine, 53, is a complex organism. Friends describe him as a Renaissance Man, but he's more. He's Renaissance Man, Research Nerd and Neuromancer rolled into one.
"When historians look back on the history of the human race," says his younger brother, Eric, chief scientist for the Walt Disney Co., "Bill's work will have a greater effect on civilization than the Industrial Revolution. . . . Environmental forces have governed our evolution for 4 billion years. But in the future we'll be governed by human science."
"What is distinguishing about Bill is his combination of drive and intelligence," says friend and former colleague Robert Gallo, the co-discoverer of HIV, the virus that causes AIDS, who now heads the Institute of Human Virology in Baltimore. "I don't know anyone else who operates at quite that level."
Haseltine also draws fire.
Robert Cook-Deegan, author of "Gene Wars," points out that Haseltine has a "titanic ego."
Someone who has known Haseltine a long time says, "Very few people who know or meet Bill actually like him."
"That fact," says one of the Haseltine clan, "is not entirely unknown to the family."
William Haseltine says this: "If you're successful, they hate you."
On many fronts, Haseltine is successful.
He entertains senators and scientists in his capacious home in Georgetown. His driver swings by a McLean athletic club so that Haseltine, in his Harvard warm-up suit, can hit winners against a tennis ball machine. He schmoozes with power-pals at Jack Valenti's celebrity film screenings.
He wears wire-rim glasses and a simple wedding band.
With a gentle smile, a slight lisp and self-confidence bordering on arrogance, he holds forth on the beauty of 11th-century Hindu bronzes, the subtleties of single-malt Scotch, the strengths of a '56 Thunderbird, the shortcomings of the National Football League, the thrill of stalking wild boar in Morocco with Xavier Guerrand-Hermes of scarf fame.
"He knows a lot about everything," says his glamorous wife, Gale Hayman, who runs a cosmetics company in New York. She and her first husband had a shop called Giorgio on Rodeo Drive in Beverly Hills. She launched a perfume, also called Giorgio, that became the best-selling, if not the best-smelling, fragrance ever. She reportedly brought about $90 million to their made-for-the-millennium marriage in 1991.
Haseltine and Hayman divide their time between Washington and New York. "We try never to spend more than two nights in a row apart from each other," Hayman says.
But the place where Haseltine seems most comfortable in his success is at his company headquarters just off I-270 in Montgomery County. In a lab. Gazing into a petri dish full of cloned human genes.
Surrounded by some 360 scientists, tons of high-octane computers and a "lean, efficient" legal team of 10, Haseltine stands in the middle of the biomedical maelstrom. His warp-speed method of patenting genes is considered dazzling by some, disturbing by others. Because he traffics in the re-creation of life itself Haseltine is constantly faced with ethical and moral questions.
His company has an ethics advisory board, chaired by James B. Wyngaarden, former director of the National Institutes of Health. It includes opera singer Beverly Sills and Haseltine himself. But Haseltine is secure, unflinching in his beliefs of what is good and what is evil. He says he wants to cure diseases and make lots of money.
And, he is asked, is he playing God?
"I wish we were," he says.
Repro Man
He's not the kind of executive who knows the names of all his employees.
Many of his employees, in fact, don't even have names. They are robots.
With the help of rows and rows of robotic arms -- swiveling to and fro with pipettes and large petri dishes -- the scientists at Human Genome Sciences identify, characterize and catalogue human genes at a rapid-fire pace.
To determine the codes of the genes, Haseltine says, "we've built our own sequencing equipment. We can catalogue more than 20,000 genes a day. I remember when we were lucky to do one a year."
In one dim room full of General Electric freezers rest more than 2 million samples of human genes.
Genes are identified by distinct codes. Once Haseltine isolates a specific gene and discovers a medical use for that gene, he applies for a patent. He then hopes to do one of four things with that patented gene: use the gene as medicine, as in VEGF-1; manufacture the protein that the gene makes for use as a drug; provide the gene to pharmaceutical companies and academic labs for drug development; or use the genes to fashion a blood test that can predict or detect disease. HGS stands to make a killing in each case.
If the protein from a gene or the gene itself can be used as medicine, the drug could be worth billions of dollars. One protein cure, for example, can be used to grow skin to heal large wounds that would not normally heal.
Millions more may be made from using genes that predict diseases. HGS has isolated three genes that, when mutated, predispose people to colon cancer, the most frequent form of inherited cancer.
The human body contains between 80,000 and 150,000 distinct genes. Of these, HGS has partial copies of 95 percent and has isolated full-length copies of about 75 percent, Haseltine says. In the beginning, critics called Haseltine down for applying for patents on partial gene sequences before he fully understood the gene's potential.
"Since we've isolated most of the human genes by 1994, the vast majority of our effort is devoted to understanding and developing the medical applications of the genes," Haseltine says.
Other labs -- such as Insight in Palo Alto, Calif., and Genset in France -- are competing with HGS to patent as many genes as possible. University scientists are filing patents also. Merck, the New Jersey-based pharmaceutical company, has pumped millions of dollars into a sequencing project at Washington University in St. Louis.
But Haseltine is way ahead of the pack. His computer wizards have created software that allows scientists to swiftly survey, compare and discern the genetic composition of cells.
"The only organization that comes close to HGS in filing patents on genes and their medical uses is NIH," Haseltine says. Last year, NIH filed 125 patents; HGS filed about 200.
"Genes share the magical properties of life," according to the company's 1996 annual report. "Like seeds, when cultivated, genes produce an unlimited supply of the inherited entity; one gene -- one protein. It is the individual amplified gene and its protein product that is the essential tool of pharmaceutical discovery."
And so, Haseltine is building a world-changing pharmaceutical company in Rockville.
So far he's raised some $550 million, he says. SmithKline Beecham ponied up $125 million in 1993. Other companies have followed. He believes strongly that his research is the catalyst for the recent mega-merger talks between SmithKline and Glaxo Wellcome. Through contracts and alliances with pharmaceutical labs, HGS earned $36 million last year.
"He's very arrogant and he's also impatient," says Robert Cook-Deegan, author of "The Gene Wars." "That's one of the reason the venture capital folks like him. He's very focused. A lot of those people do make waves."
Not everyone is convinced that Haseltine's future is roses. Stephen G. Pagliuca, managing director of Bain Capital, a Boston consulting firm, told Business Week that "investing in genomics is like going to Las Vegas."
There is also concern among the scientific community that by focusing on the utilitarian aspects of a gene -- and its marketability -- scientists will fail to completely research the gene and discover all its possibilities and pitfalls.
"I'm not against patents," says Bartha Maria Knoppers, professor of law at the University of Montreal and chairman of the ethics committee of the Human Genome Project at NIH. "I just hope the patenting process doesn't close doors prematurely. Companies such as Haseltine's could impede the earlier sharing of research results."
Haseltine bristles at such criticism. "That's a deep misunderstanding of the patent process, which is designed to make public discoveries of commercial importance so that others may build on that knowledge to open new fields."
Speaking about "the companies like HGS who've gone out there and done the gene hunting," Isner says: "It's not an exaggeration to relate that to Magellan or Lewis and Clark . . . to see what was here. Until you identify the genes that exist in nature, you can't even begin to be intelligent about designing contemporary therapies."
Though "in a utopian universe," said one scientist who works with Haseltine and asked that his name not be used, "it might be preferable to not allow one man to patent genes at all."
Born to Be Wired
William Alan Haseltine came to genetic fruition in 1944. His father, William R. Haseltine, was a scientist at the Naval Weapons Center at China Lake, Calif.
One of the first words, and homonyms, little Bill heard was the name of his mother: Jean.
"He wants to be a big shot and he is. He wanted to live in luxury and he does. He's a very great scientist on his own," says his father, William R. Haseltine, 87, who is retired, living in California and reading books such as the Encyclopedia of the Eye.
"My mother told me I was one of the first people saved by penicillin," the younger Haseltine says. "I had pneumonia. I was 4 months old. Doctors said I would have died without it. I guess I owe my life to penicillin."
Jean Adele Haseltine taught French off and on. She battled a host of health problems ranging from detached retinas to manic depression. "We were very close," Haseltine says.
While he was in elementary school, his mother contracted psoriasis on her hand, which led to blood poisoning. Young Bill watched as she lay in bed, her hand soaking in Epsom salts, red streaks streaming up her arm. "Are you going to die?" he asked her.
Another recollection: When he was a Boy Scout, he and a friend were climbing a mountain near the Navy base. "I raced up, of course, because I wanted to be first."
"I was an A-plus student," Haseltine recalls. "I was a super-achiever."
Both of his parents were scout leaders. After dinner the family read together -- Shakespeare plays, Greek tragedies.
"I don't remember any of that," counters Florence, Haseltine's older sister. Florence Haseltine is the director of the Center for Population Research at the National Institute of Child Health and Human Development in Washington. She is also president of her own company, the Haseltine Corp., which makes protective traveling cases for wheelchairs.
"Things were tough when we were kids," Florence Haseltine recalls. "My mother was sick a lot. My father had to raise four kids in the desert."
"He would come home every night for dinner," Florence says of her father. "He would work on his physics. We didn't interact much after dinner."
"I intentionally don't remember anything about my childhood," she says.
She does recall being 13 and finding her mother in a pool of blood. Soon after the attempted suicide Jean Haseltine began to take an antidepressant.
The good times her brother remembers, Florence says, must have occurred after her mother was put on medication.
In the spring of 1981, Jean Haseltine took her own life. But, Florence points out, treatment gave her mother 20 bonus years. Florence is matter-of-fact. "Mother was saved by modern medicine."
Apostolic Succession
He believes in himself.
"We're ushering in a new era of regenerative medicine," he says. "The future of medicine is human proteins and human genes."
And Haseltine believes he is the one person who can grasp the omnipotent power, the burning glory of gene-based drugs. He believes he is the one chosen to lead humankind into the promised land.
He may be. After all, he is the latest in an astounding line of renowned scientists. The pictures of his mentors hang on the wall of his office: Chemist George Pimentel, who has a hall named after him at the University of California, Berkeley; James D. Watson, who won the 1962 Nobel Prize for medicine for his discovery of the molecular structure of DNA; Walter Gilbert, who won the 1980 Nobel Prize for chemistry; and David Baltimore, who won the 1975 Nobel Prize for medicine.
A "very, very serious" freshman in Berkeley in 1962 -- "I polished my shoes and wore a jacket and tie to class" -- Haseltine was among the "15 brightest students" selected by Pimentel to have a weekly lunch with Nobel laureates. "I was headed toward medicine," Haseltine says. "Pimentel turned me toward science."
At nearly every juncture in his scientific ascent, Haseltine made a decision or a discovery or a dumb mistake that moved him closer to his destiny.
In graduate school at Harvard, he studied the properties of bacteria in the lab of Watson and Gilbert. Haseltine was instructed by his masters to discover how bacteria reproduce. He remembers the intense battle to see who could discover the conditions first. He was competing with a professor in the lab next door. "The professor even sent his grad student in to read my notebooks," Haseltine recalls. "Gilbert was even telling the professor what I was doing."
When Haseltine asked his adviser for protection, Gilbert said, "This way, Bill, the answer will come faster. You may get it. He may get it. But science will be the better."
Haseltine and a colleague won the race.
He says with a wide grin, "I could re-create part of life."
He shakes his head, "It took me 24 hours a day, 6 1/2 days a week. I wore the same pair of brown corduroy pants for a year and half. Never washed them."
"That's the one time in my life that I felt I really worked to capacity."
This exploration of how an organism regulates its behavior foreshadowed the work he does today.
In the lab of David Baltimore, Haseltine studied retroviruses.
"I made a number of novel and startling discoveries," he says.
For one thing, he says, with some delight, "I proved Harold Varmus wrong about the means by which a virus begins its replication process. He said it was one thing, we said it was another. We were right; he was wrong."
Today Varmus is head of the National Institutes of Health. He refused to talk about Haseltine for this story.
"Really great people believed in me all the way," Haseltine says. "I picked them, I guess they had to pick me."
Standing on the shoulders of these giants, Haseltine had a chance to strut his wide-ranging stuff -- intelligence, discipline, skepticism and a go-for-the-jugular competitive streak.
For 17 years Haseltine taught and researched at the Dana Farber Cancer Institute at Harvard University. In 1979, while collaborating with Robert Gallo, Haseltine discovered the way the first known human retrovirus caused leukemia. "I was already known for my work on bacteria and DNA damage and repair, but that made me very famous," he says. "I was a pretty well-known guy."
With Gallo and a few others, Haseltine in 1982 created the hypothesis that AIDS was caused by a retrovirus. They turned out to be correct.
"I did a lot of novel work on the AIDS virus," Haseltine says.
Gallo says, "Bill needs to say how good he is when it's evident."
But Gallo remembers those years fondly. "He provided a considerable amount of momentum, energy and leadership."
He adds, "Bill has his quirks."
As Haseltine, the resolute researcher, hassled with test tubes and Bunsen burners, he watched his mentors and friends, one by one, branch out from academia into private enterprise. "We had a car that was so dented, you had to climb in through the window," he recalls.
The scientists, he recalls, were extremely territorial. "We fought over offices that were the size of broom closets."
Research took him to Houston in 1981. When he walked into the spacious lobby of an oil company, he was struck by the absurdity of it all -- oil companies feasted while hard-working academic scientists squabbled over crumbs. Scales fell from Haseltine's eyes.
"Knowledge comes from universities," he says. "Drugs come from pharmaceutical companies."
Haseltine began to dip his toe in entrepreneurial waters. While still teaching at Harvard, he helped launch a handful of biotech companies. One day a venture capitalist in New York called. "I've finally found something to get you out of Harvard."
Haseltine flew to Washington. Over hamburgers and Cokes at the food court above the Bethesda Metro, he met a scientist from the National Institutes of Health. J. Craig Venter was developing a way to identify and sequence genes.
Venter had also been involved in the Human Genome Project -- a federally funded effort to map human DNA and to explore the causes of genetically linked diseases. In his quiet way Venter explained his process to Haseltine.
"It took me about 10 minutes to see the future," Haseltine says today. And the future was Human Genome Sciences, a company that would use sophisticated computer programs and specially designed robots to look at genes in a different way from the Human Genome Project. Whereas the project was interested in studying how genes cause disease, Haseltine says, HGS would study how genes can cure disease. And make a mess of money in the process.
Sold on the dream, Venter left NIH and the two men went to work together. Venter isolated the genes and Haseltine, using robotics and computers, discovered their purposes.
The partnership was unlikely.
"There was conflict from the very beginning," says Cook-Deegan.
Razzle-dazzle Haseltine, the high-on-himself hotshot from Harvard, and Venter the quiet, studious former surfer, never adapted to one another.
Founded in 1992, the company was high-profile. So was the inevitable divorce in 1997. Venter continues to explore the structure of genes at his lab called the Institute for Genomic Research.
About Haseltine, Venter would not comment.
Of Venter, Haseltine says, "He doesn't really care about alleviating human suffering. He's in it for the science . . . the evolution."
That debate, Haseltine adds, was at the heart of their split. "We had different goals."
Capital Investment
Washington, William Haseltine says, is the perfect place for him to be. He finds the city full of bright, fascinating people. And not all of them are politicians.
He says that "20 percent of America's high-technology companies are in the mid-Atlantic region. My being in Washington is part of that."
And the socializing that he and Hayman do, he says, is for pleasure, not for networking.
Haseltine and Hayman lead a swirling social life in New York and in Washington.
They run in celebrity circles -- supping with actor Michael York, drinks with developer and publisher Mortimer Zuckerman, lunching with his dealmaking superlawyer Lloyd Cutler and Cutler's wife, Polly Kraft, a painter.
"I do not qualify for my brother's social set," says Florence Haseltine.
Polly Kraft says, "Bill's a great, great guest. His interests are very catholic and wide. He reads. He has opinions on just about everything, from Cezanne to cloning. Gale is involved in a completely other world. She's a very good marketer. She's written her own book about beauty. Both are full of life."
Still, Haseltine says, it's hard for him to carry on conversations in Washington. "The way I talk is not the way others talk," he says. "I always question. That's not polite."
On this night at Mortimer's, a small Upper East Side Manhattan cafe where CBS honcho Don Hewitt dines near movie producer Alan J. Pakula, Haseltine and his wife look right at home.
"Gale has super-glitz," says Haseltine.
"I love talking to scientists," says Hayman. "They question you, they listen to you."
At first glance, she seems like a trophy wife, a noble prize for the research scientist turned entrepreneur. But Hayman is every bit as ambitious as her husband.
They met in Hollywood at a black-tie dinner. He was a power-driven professor at Harvard; she a stylish businesswoman. Mortimer Zuckerman was president of the Dana Farber Cancer Institute board of trustees while Haseltine was there. Of Haseltine and Hayman, Zuckerman said: "Their success outside the academic world turned the people of Cambridge various shades of green."
Haseltine delights in recounting his wife's amazing past -- nearly as amazing as his own. An only child, Hayman grew up in New York in a brownstone on East 54th Street. Her father, a soldier and a model for Brylcreem, died when she was a year old. Hayman was trained as a ballerina at the American School of Ballet. She also posed as a model for Simplicity patterns. She remembers skating at Rockefeller Center and going to St. Thomas's Episcopal Church.
When she was a teenager, her mother moved to California. Hayman enrolled in a ballet school there, but discovered the first day that the studio was shoddy and the teacher was tipsy. Eventually she married and she and her first husband opened Giorgio, the chi-chi shop in Beverly Hills that put the styles in the lifestyles of the rich and famous. In 1981, she created the Giorgio fragrance that soared to yearly sales of $100 million.
"When we got married," Haseltine is quick to say, "I had made millions, too."
Haseltine, the chemist, explains that Hayman's perfume was "built to project." It was the right fragrance for the right time, he says, because as baby boomers age, "the older women lose their sense of smell, so they put on more fragrance. That's why we associate old women with strong perfume."
After Hayman divorced, Giorgio was sold to Avon Products. She started her own company, Gale Hayman Beverly Hills. In 1996 she published a beauty book, "How Do I Look? From Cosmetics to Confidence." Today Hayman sells her wares on Home Shopping Network and writes a syndicated newspaper column.
Looks matter to Haseltine and Hayman. At one point the conversation turns to a possible cooperation between the two companies -- Human Genome Sciences and Gale Hayman cosmetics.
"We're interested right now in medical uses, not cosmetic uses," Haseltine says. But he says that genes can be developed in his lab to create healthier, younger, smoother skin. Or to cure baldness.
"Our fields may actually converge," he says, "five or 10 years from now."
He believes that a human's natural life span is 120 years, "if we don't get disease and keep ourselves in good shape." We are already becoming a "society of older, still-productive people," he says. "People care about how they look when they're in their seventies."
As if on cue, a turbaned older woman at the next table rises and wishes them good night. She's Leah Maria, the wife of Boutros Boutros-Ghali.
With Hayman, as with nearly everyone, Haseltine is terminally pedagogical. He finishes her sentences. She doesn't seem to mind.
"He has an amazing memory," she says. "He remembers every minute detail."
They share an appreciation for fine things. One night, for kicks, they thumbed through a stack of Sotheby's catalogues, perusing thousands of items. They each picked their 50 favorite objets d'art. "We were concordant on 45," he says.
They also differ. "Bill is totally against capital punishment," Hayman says. "I have a question mark."
"I like rough-and-tumble intellectual arguments," he says. "She likes smoother conversations."
And they differ on the Big Question. "I like to think there's a higher power," Hayman says. "I don't question it that much."
Asked if he's seduced by his wife's faith, Haseltine says, "Not particularly."
"I'm not religious," he says at one point, "I'm philosophical." He's fascinated by man's relationship to the universe. But he loses interest "at the point at which it becomes religion."
"If there is a God, He's not interested in man. So what difference does it make?"
As a result, he adds, man must take matters into his own hands.
He Rests
On the shuttle flight from Boston to Washington, Haseltine sits in the emergency exit row. He enjoys the extra leg room and doesn't mind the added responsibility.
It's been a good day. He's made the rounds among venture capital firms. He's seen evidence at St. Elizabeth's of Joseph Isner's astounding work. He's learned from the home office that the Food and Drug Administration has approved initial clinical trials of the first of what he hopes could be hundreds of new gene-based drugs. He's hitting winners right and left.
"This is a red-letter day," he says.
The world he is returning to in the evening has changed significantly from the world he left in the morning. He glances at a newspaper and at a recent issue of Science magazine. Both publications are alive with stories of genetic discovery.
He is asked what it is like to be both admired and disliked.
Taking a deep breath, he gets philosophical for a moment. "Do not care about your enemies," he says. What is done is done for the sake of advancing science. "We are trained to compete in a brutal and vicious way."
Far below the plane, lights twinkle and members of the human race move about like unexplored stars.
William Haseltine leans back in his seat. He dreams. |
